Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer death in the United States. Lethality of PDA owes largely to the advanced disease stage at the time of diagnosis and to its profound resistance to existing therapies. Targeted therapy is a cornerstone of precision medicine, and is currently the focus of much anticancer drug development. However, in the context of pancreatic cancer, no chemical inhibitors exist for the most common KRAS mutations (G12D, G12V) even though it is well established that the oncogenic KRAS promotes drug resistance. Thus, a detailed understanding of the role of specific genetic lesions and their signaling surrogates in the initiation and progression of PDA is critical to improving treatment efficacy and patient outcome for this disease.

Our goal is to utilize sophisticated genetically engineered mouse models and ex vivo culture systems to understand the basic mechanisms underlying PDA redox biology such that vulnerabilities can be identified and tested for therapeutic intervention.